A tax on luxury : HTLV - I infection of CD 4 + CD 25 + Tregs

1144 The Journal of Clinical Investigation http://www.jci.org Volume 115 Number 5 May 2005 mal scarring (8). Some of the clinical features of EDS are actually evident in the families with ICH studied by Gensure et al. (6), and this makes sense. But the reason why some ICH patients also develop acute bone lesions at a specific age is not clear. The authors hypothesize that periosteum is only loosely attached to the underlying bone structure in infants and that periosteum detachment (perhaps facilitated by the collagen mutation) would be the primum movens leading to increased bone formation. Such a hypothesis is not entirely consistent with the histologic studies done sequentially in cases of ICH (3), which clearly indicate that inflammation is the initial event, in agreement with the clinical and PGErelated observations. It is noteworthy that Gensure et al. found that 79% of the individuals studied who were heterozygous for the COL1A1 mutation had an episode of cortical hyperostosis, while 21% of the subjects carrying the R836C substitution do not develop disease, which confirms the clinically observed reduced penetrance at the molecular level. Many unresolved questions regarding the pathology of this disease may have to wait for the engineering of an appropriate mouse model. In conclusion, by showing convincingly that Caffey disease is associated with a COL1A1 missense mutation, Gensure et al. (6) have once again demonstrated the power of linkage analysis. They have lifted the lid of a black box, but what is inside the box remains to be discovered.